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Diffuse intrinsic pontine glioma (DIPG) is a universally fatal pediatric brain tumor. We have previously shown that the brain penetrant class 1 HDAC inhibitor RG2833 (RGFP109) inhibits cell growth (MTS assay for HSJD007 p=0.0004, JHH-DIPG1 p=0.001, SF-7761 p=0.04, SU-DIPG13 p=0.01 by t-test), reduces proliferation (phospho-Rb Western blot, BrdU immunofluorescence HSJD007 p=0.008, JHH-DIPG1 p=0.0002 by t-test), and induces apoptosis (cPARP Western blot, cleaved caspase 3 immunofluorescence HSJD007 p20). Evaluation of combination treatment for apoptotic effects in vitro and in vivo are ongoing. These findings identify RG2833 and Paxalisib as a promising combination therapy for DIPG. Citation Format: Katherine Barnett, Hyuk Jean Kwon, Orlandi Novak, Charles Eberhart, Eric Raabe. Brain penetrant HDAC and PI3K/mTOR inhibitors synergize to induce DIPG cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3987. |
